The classical view that renin is an enzyme with a fixed specific activity and the plasma renin activity is regulated solely by physiological secretory mechanism require drastic revisions in view of discovery of various forms of activatable prorenin. Understanding of the regulation of renin requires comprehensive knowledge concerning the synthesis of its precursors, their processing and activation. Such studies, in turn, should be supported by solid information on the structure of renin and precursors. Our current views on the nature and identity of renin and various precursors, their mutual relationship and regulatory mechanism involving these precursors are very confusing. Basically this is due to a large gap in our knowledge of structure of renin and precursors. This deficiency is largely due to lack of a sufficient quantity of pure renin. Since we now have developed a large scale purification method for renin, have identified its active site resembling that of aspartyl proteases, and have determined a part of its amino acid sequence, we are in the position to completely determine the total structure of mouse submaxillary gland renin. We plan to extend this study to the identification of specific features of renal renin of the rat and/or mouse by peptide mapping. Approaches will be made to clarify the identify of the putative preprorenin prepared by in vitro synthesis using mRNA by radiolabeling and identifying amino terminal residues and hopefully amino terminal sequence to see if it contains a signal sequence. Attempt to identify characteristic structure of renin inhibitory structure in prorenin will be initiated. These structural studies are expected to provide an acutely needed structural information in renin studies thus making important contribution in clarifying many puzzling problems. It will also facilitate rational approach to the design of inhibitors of renin useful for diagnostic purposes.